Studies on the induction of sex-linked recessive lethal mutations in Drosophila melanogaster by nitroheterocyclic compounds.
24 nitroheterocyclic compounds were investigated for their capacity to induce sex-linked recessive lethals in Drosophila, by the adult feeding technique, and in some cases injection or larval-feeding methods. Out of 9 5-nitroimidazoles, ZK 26.173 and ZK 25.095 (moxnidazole) were clearly active whereas nimorazole and ronidazole were marginally mutagenic. Out of 10 5-nitrofurans, nitrovin, furazolidone and furaltadone were unambiguously mutagenic, whereas nitrofurantoin was a borderline case. Nitrofurans were active at lower molar concentrations than nitroimidazoles. Out of a group of 5 related nitro compounds (2 nitrothiophenes, picrolonic acid, niridazole and 4-NQO), only 4-NQO was clearly mutagenic, when fed to larvae. Experiments with germ-free flies showed that, for ZK 26.173 and furazolidone, the gut flora of Drosophila do not play a role in the activation of the compounds to mutagenic metabolites. Furazolidone, 4-NAO, ZK 26.173, ZK 25.095 and furaltadone were tested in mal and cin strains, both of which lack xanthine dehydrogenase and aldehyde oxidase. The latter enzyme and xanthine oxidase are known to carry out nitro reduction in mammalian tissues. For ZK 26.173, the mutation frequencies were drastically reduced in the enzyme-deficient strains, indicating the involvement of one of these enzymes in the activation of this substance.
D000818:Animals; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000201:enzymology / Q000382:microbiology; D005260:Female; D005804:Genes, Lethal; D005808:Genes, Recessive; D005856:Germ-Free Life; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D007422:Intestines / Q000382:microbiology; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D009574:Nitro Compounds / Q000494:pharmacology*; D010088:Oxidoreductases / Q000172:deficiency; D014960:X Chromosome
D006571:Heterocyclic Compounds; D009153:Mutagens; D009574:Nitro Compounds; D010088:Oxidoreductases